Immunotherapy in Bladder Cancer: Current Methods and Future Perspectives

Mikołaj Wołącewicz, Rafał Hrynkiewicz, Ewelina Grywalska, Tomasz Suchojad, Tomasz Leksowski, Jacek Roliński, Paulina Niedźwiedzka-Rystwej, Mikołaj Wołącewicz, Rafał Hrynkiewicz, Ewelina Grywalska, Tomasz Suchojad, Tomasz Leksowski, Jacek Roliński, Paulina Niedźwiedzka-Rystwej

Abstract

Bladder cancer is one of the most significant genitourinary cancer, causing high morbidity and mortality in a great number of patients. Over the years, various treatment methods for this type of cancer have been developed. The most common is the highly efficient method using Bacillus Calmette-Guerin, giving a successful effect in a high percentage of patients. However, due to the genetic instability of bladder cancer, together with individual needs of patients, the search for different therapy methods is ongoing. Immune checkpoints are cell surface molecules influencing the immune response and decreasing the strength of the immune response. Among those checkpoints, the PD-1 (programmed cell death protein-1)/PD-L1 (programmed cell death protein ligand 1) inhibitors aim at blocking those molecules, which results in T cell activation, and in bladder cancer the use of Atezolizumab, Avelumab, Durvalumab, Nivolumab, and Pembrolizumab has been described. The inhibition of another pivotal immune checkpoint, CTLA-4 (cytotoxic T cell antigen), may result in the mobilization of the immune system against bladder cancer and, among anti-CTLA-4 antibodies, the use of Ipilimumab and Tremelimumab has been discussed. Moreover, several different approaches to successful bladder cancer treatment exists, such as the use of ganciclovir and mTOR (mammalian target of rapamycin) kinase inhibitors, IL-12 (interleukin-12) and COX-2 (cyclooxygenase-2). The use of gene therapies and the disruption of different signaling pathways are currently being investigated. Research suggests that the combination of several methods increases treatment efficiency and the positive outcome in individual.

Keywords: bladder cancer; checkpoint inhibitor; immunotherapy.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effect of checkpoint inhibitors in bladder cancer treatment. PD-1/PD-L1 and CTLA-4 blockers interfere with the immune system’s inhibitory checkpoint molecules, leading to T cell activation and tumor cell death. APC: antigen-presenting cells.

References

    1. Ferlay J., Ervik M., Lam F., Colombet M., Mery L., Pińeros M., Znaor A., Soerjomataram I., Bray F., editors. Cancer Today (powered by GLOBOCAN 2018) IARC CancerBase No. 15. IARC; Lyon, France: 2018.
    1. Kim H.S., Seo H.K. Immune checkpoint inhibitors for urothelial carcinoma. Investig. Clin. Urol. 2018;59:285–296. doi: 10.4111/icu.2018.59.5.285.
    1. Saginala K., Barsouk A., Aluru J.S., Rawla P., Padala S.A., Barsouk A. Epidemiology of Bladder Cancer. Med. Sci. 2020;8:15. doi: 10.3390/medsci8010015.
    1. Iliou A., Panagiotakis A., Giannopoulou A.F., Benaki D., Kosmopoulou M., Velentzas A.D., Tsitsilonis O.E., Papassideri I.S., Voutsinas G.E., Konstantakou E.G., et al. Malignancy Grade-Dependent Mapping of Metabolic Landscapes in Human Urothelial Bladder Cancer: Identification of Novel, Diagnostic, and Druggable Biomarkers. Int. J. Mol. Sci. 2020;21:1892. doi: 10.3390/ijms21051892.
    1. Chien T.-M., Chan T.-C., Huang S.-H., Yeh B.-W., Li W.-M., Huang C.-N., Li C.-C., Wu W.-J., Li C.-F. Role of Microtubule-Associated Protein 1b in Urothelial Carcinoma: Overexpression Predicts Poor Prognosis. Cancers. 2020;12:630. doi: 10.3390/cancers12030630.
    1. Jagodinsky J.C., Harari P.M., Morris Z.S. The Promise of Combining Radiation Therapy with Immunotherapy. Int. J. Radiat. Oncol. Biol. Phys. 2020 doi: 10.1016/j.ijrobp.2020.04.023.
    1. National Cancer Institute. [(accessed on 28 April 2020)]; Available online: .
    1. Fyfe G.A., Fisher R.I., Rosenberg S.A., Sznol M., Parkinson D.R., Louie A.C. Long-term response data for 255 patients with metastatic renal cell carcinoma treated with high-dose recombinant interleukin-2 therapy. J. Clin. Oncol. 1996;14:2410–2411. doi: 10.1200/JCO.1996.14.8.2410.
    1. Atkins M.B., Lotze M.T., Dutcher J.P., Fisher R.I., Weiss G., Margolin K., Sznol M., Parkinson D., Hawkins M., Paradise C., et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: Analysis of 270 patients treated between 1985 and 1993. J. Clin. Oncol. 1999;17:2105–2116. doi: 10.1200/JCO.1999.17.7.2105.
    1. European Association of Urology EAU Guidelines on Non-Muscle-Invasive Bladder Cancer (TaT1 and CIS) [(accessed on 28 April 2020)];2019 Available online: .
    1. Farina M.S., Lundgren K.T., Bellmunt J. Immunotherapy in Urothelial Cancer: Recent Results and Future Perspectives. Drugs. 2017;77:1077–1089. doi: 10.1007/s40265-017-0748-7.
    1. Morales A., Eidinger D., Bruce A.W. Intracavitary Bacillus Calmette-guerin in the Treatment of Superficial Bladder Tumors. J. Urol. 1976;116:180–182. doi: 10.1016/S0022-5347(17)58737-6.
    1. Song D., Powles T., Shi L., Zhang L., Ingersoll M.A., Lu Y.J. Bladder cancer, a unique model to understand cancer immunity and develop immunotherapy approaches. J. Pathol. 2019;249:151–165. doi: 10.1002/path.5306.
    1. Lamm D.L., Thor D.E., Harris S.C., Reyna J.A., Stogdill V.D., Radwin H.M. Bacillus Calmette-Guerin immunotherapy of superficial bladder cancer. J. Urol. 1980;124:38–40. doi: 10.1016/S0022-5347(17)55282-9.
    1. Zhang C., Berndt-Paetz M., Neuhaus J. Identification of Key Biomarkers in Bladder Cancer: Evidence from a Bioinformatics Analysis. Diagnostics. 2020;10:66. doi: 10.3390/diagnostics10020066.
    1. Abugomaa A., Elbadawy M., Yamawaki H., Usui T., Sasaki K. Emerging Roles of Cancer Stem Cells in Bladder Cancer Progression, Tumorigenesis, and Resistance to Chemotherapy: A Potential Therapeutic Target for Bladder Cancer. Cells. 2020;9:235. doi: 10.3390/cells9010235.
    1. Batista R., Vinagre N., Meireles S., Vinagre J., Prazeres H., Leão R., Máximo V., Soares P. Biomarkers for Bladder Cancer Diagnosis and Surveillance: A Comprehensive Review. Diagnostics. 2020;10:39. doi: 10.3390/diagnostics10010039.
    1. Degeorge K., Holt H., Hodges S. Bladder Cancer: Diagnosis and Treatment. Am. Fam. Physician. 2017;96:507–514.
    1. Bellmunt J., Orsola A., Leow J.J., Wiegel T., De Santis M., Horwich A. Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2014;25:iii40–iii48. doi: 10.1093/annonc/mdu223.
    1. Borkowska E.M., Konecki T., Pietrusiński M., Borowiec M., Jabłonowski Z. MicroRNAs Which Can Prognosticate Aggressiveness of Bladder Cancer. Cancers. 2019;11:1551. doi: 10.3390/cancers11101551.
    1. Crispen P.L., Kusmartsev S. Mechanisms of immune evasion in bladder cancer. Cancer Immunol. Immunother. 2019;69:3–14. doi: 10.1007/s00262-019-02443-4.
    1. De Boer E.C., De Jong W.H., Steerenberg P.A., Aarden L.A., Tetteroo E., De Groot E.R., Van der Meijden A.P.M., Vegt P.D.J., Debruyne F.M.J., Ruitenberg E.J. Induction of urinary interleukin-1 (IL-1), IL-2, IL-6, and tumour necrosis factor during intravesical immunotherapy with bacillus Calmette-Guérin in superficial bladder cancer. Cancer Immunol. Immunother. 1992;34:306–312. doi: 10.1007/BF01741551.
    1. Luo Y., Chen X., O’Donnell M.A. Mycobacterium bovis bacillus Calmette-Guérin (BCG) induces human CC- and CXC-chemokines in vitro and in vivo. Clin. Exp. Immunol. 2006;147:370–378. doi: 10.1111/j.1365-2249.2006.03288.x.
    1. Kawai K., Miyazaki J., Joraku A., Nishiyama H., Akaza H. Bacillus Calmette-Guerin (BCG) immunotherapy for bladder cancer: Current understanding and perspectives on engineered BCG vaccine. Cancer Sci. 2013;104:22–27. doi: 10.1111/cas.12075.
    1. Biot C., Rentsch C.A., Gsponer J.R., Birkhauser F.D., Jusforgues-Saklani H., Lemaitre F., Auriau C., Bachmann A., Bousso P., Demangel C., et al. Preexisting BCG-Specific T Cells Improve Intravesical Immunotherapy for Bladder Cancer. Sci. Transl. Med. 2012;4:137ra72. doi: 10.1126/scitranslmed.3003586.
    1. Brandau S., Riemensberger J., Jacobsen M., Kemp D., Zhao W., Zhao X., Jocham D., Ratliff T.L., Böhle A. NK cells are essential for effective BCG immunotherapy. Int. J. Cancer. 2001;92:697–702. doi: 10.1002/1097-0215(20010601)92:5<697::AID-IJC1245>;2-Z.
    1. Siracusano S., Vita F., Abbate R., Ciciliato S., Borelli V., Bernabei M., Zabucchi G. The Role of Granulocytes Following Intravesical BCG Prophylaxis. Eur. Urol. 2007;51:1589–1599. doi: 10.1016/j.eururo.2006.11.045.
    1. Suttmann H., Riemensberger J., Bentien G., Schmaltz D., Stöckle M., Jocham D., Böhle A., Brandau S. Neutrophil Granulocytes Are Required for Effective Bacillus Calmette-Guérin Immunotherapy of Bladder Cancer and Orchestrate Local Immune Responses. Cancer Res. 2006;66:8250–8257. doi: 10.1158/0008-5472.CAN-06-1416.
    1. Ratliff T.L., Ritchey J.K., Yuan J.J.J., Andriole G.L., Catalona W.J. T-Cell Subsets Required for Intravesical BCG Immunotherapy for Bladder Cancer. J. Urol. 1993;150:1018–1023. doi: 10.1016/S0022-5347(17)35678-1.
    1. Batista R., Lima L., Vinagre J., Pinto V., Lyra J., Máximo V., Santos L., Soares P. TERT Promoter Mutation as a Potential Predictive Biomarker in BCG-Treated Bladder Cancer Patients. Int. J. Mol. Sci. 2020;21:947. doi: 10.3390/ijms21030947.
    1. De Boer E.C., De Jong W.H., Van Der Meijden A.P.M., Steerenberg P.A., Witjes J.A., Vegt P.D.J., Debruyne F.M.J., Ruitenberg E.J. Presence of activated lymphocytes in the urine of patients with superficial bladder cancer after intravesical immunotherapy with bacillus Calmette-Guérin. Cancer Immunol. Immunother. 1991;33:411–416. doi: 10.1007/BF01741603.
    1. Pryor K., Goddard J., Goldstein D., Stricker P., Russell P., Golovsky D., Penny R. Bacillus Calmette-Guerin (BCG) enhances monocyte- and lymphocyte-mediated bladder tumour cell killing. Br. J. Cancer. 1995;71:801–807. doi: 10.1038/bjc.1995.155.
    1. Pettanati C., Ingersol M.A. Mechanisms of BCG immunotherapy and its outlook for bladder cancer. Nat. Rev. Urol. 2018;15:615–625. doi: 10.1038/s41585-018-0055-4.
    1. Lamm D.L., Blumenstein B.A., Crissman J.D., Montie J.E., Gottesman J.E., Lowe B.A., Sarosdy M.F., Bohl R.D., Grossman H.B., Beck T.M., et al. Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: A randomized Southwest Oncology Group Study. J. Urol. 2000;163:1124–1129. doi: 10.1016/S0022-5347(05)67707-5.
    1. Askeland E.J., Newton M.R., O’Donnell M.A., Luo Y. Bladder cancer immunotherapy: BCG and beyond. Adv. Urol. 2012;2012:181987. doi: 10.1155/2012/181987.
    1. Sylvester R.J., van der Meijden A.P., Witjes J.A., Kurth K. Bacillus calmette-guerin versus chemotherapy for the intravesical treatment of patients with carcinoma in situ of the bladder: A meta-analysis of the published results of randomized clinical trials. J. Urol. 2005;174:86–91. doi: 10.1097/01.ju.0000162059.64886.1c.
    1. Kamat A.M., Flaig T.W., Grossman H.B., Konety B., Lamm D., O’Donnell M.A., Uchio E., Efstathiou J.A., Taylor J.A., 3rd Expert consensus document: Consensus statement on best practice management regarding the use of intravesical immunotherapy with BCG for bladder cancer. Nat. Rev. Urol. 2015;12:225–235. doi: 10.1038/nrurol.2015.58.
    1. Havel J.J., Chowell D., Chan T.A. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat. Rev. Cancer. 2019;19:133–150. doi: 10.1038/s41568-019-0116-x.
    1. Darvin P., Toor S.M., Nair V.S., Elkord E. Immune checkpoint inhibitors: Recent progress and potential biomarkers. Exp. Mol. Med. 2018;50:1–11. doi: 10.1038/s12276-018-0191-1.
    1. Liu H., Chang J.K., Hou J.Q., Zhao Z.H., Zhang L.D. Inhibition of miR-221 influences bladder cancer cell proliferation and apoptosis. Eur. Rev. Med. Pharmacol. Sci. 2017;21:3193–3199.
    1. Hindupur S.V., Schmid S.C., Koch J.A., Youssef A., Baur E.M., Wang D., Horn T., Slotta-Huspenina J., Gschwend J.E., Holm P.S., et al. STAT3/5 inhibitors suppress proliferation in bladder cancer and enhance oncolytic adenovirus therapy. Int. J. Mol. Sci. 2020;21:1106. doi: 10.3390/ijms21031106.
    1. Tsuruta M., Ueda S., Yew P.Y., Fukuda I., Yoshimura S., Kishi H., Hamana H., Hirayama M., Yatsuda J., Irie A., et al. Bladder cancer-associated cancer-testis antigen-derived long peptides encompassing both CTL and promiscuous HLA class-II-restricted Th cell epitopes induced CD4+ T cells expressing converged T-cell receptor genes in vitro. Oncoimmunology. 2018;7:e1415687. doi: 10.1080/2162402X.2017.1415687.
    1. Rink M. The landscape of genetics and biomarkers in bladder cancer. Transl. Androl. Urol. 2017;6:1027–1030. doi: 10.21037/tau.2017.11.12.
    1. Tsao J.L., Yatabe Y., Markl I.D.C., Hajyan K., Jones P.A., Shibata D. Bladder cancer genotype stability during clinical progression. Genes Chromosom. Cancer. 2000;29:26–32. doi: 10.1002/1098-2264(2000)9999:9999<::AID-GCC1002>;2-X.
    1. Rundo F., Spampinato C., Banna G.L., Conoci S. Advanced Deep Learning Embedded Motion Radiomics Pipeline for Predicting Anti-PD-1/PD-L1 Immunotherapy Response in the Treatment of Bladder Cancer: Preliminary Results. Electronics. 2019;8:1134. doi: 10.3390/electronics8101134.
    1. Alsaab H.O., Sau S., Alzhrani R., Tatiparti K., Bhise K., Kashaw S.K., Iyer A.K. PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome. Front. Pharmacol. 2017;8:561. doi: 10.3389/fphar.2017.00561.
    1. Kim T.J., Cho K.S., Koo K.C. Current Status and Future Perspectives of Immunotherapy for Locally Advanced or Metastatic Urothelial Carcinoma: A Comprehensive Review. Cancers. 2020;12:192. doi: 10.3390/cancers12010192.
    1. FDA FDA Approves New, Targeted Treatment for Bladder Cancer. [(accessed on 26 March 2020)]; Available online: .
    1. Tucker N. Avelumab Induces OS Benefit in Locally Advanced or Metastatic Urothelial Cancer. [(accessed on 26 March 2020)]; Available online: .
    1. FDA Durvalumab (Imfinzi) PATIENTS. [(accessed on 26 March 2020)]; Available online: .
    1. Sharma P., Retz M., Siefker-Radtke A., Baron A., Necchi A., Bedke J., Plimack E.R., Vaena D., Grimm M.-O., Bracarda S., et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): A multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017;18:312–322. doi: 10.1016/S1470-2045(17)30065-7.
    1. FDA FDA approves pembrolizumab for BCG-unresponsive, high-risk non-muscle invasive bladder cancer. [(accessed on 26 March 2020)]; Available online: .
    1. Galsky M.D., Wang H., Hahn N.M., Twardowski P., Pal S.K., Albany C., Fleming M.T., Starodub A., Hauke R.J., Yu M., et al. Phase 2 Trial of Gemcitabine, Cisplatin, plus Ipilimumab in Patients with Metastatic Urothelial Cancer and Impact of DNA Damage Response Gene Mutations on Outcomes. Eur. Urol. 2018;73:751–759. doi: 10.1016/j.eururo.2017.12.001.
    1. Jurkowska K., Długosz A. Research on new drugs in the therapy of bladder cancer (BC) Postepy Hig. Med. Dosw. 2018;72:442–448. doi: 10.5604/01.3001.0012.0539.
    1. Powles T., Eder J.P., Fine G.D., Braiteh F.S., Loriot Y., Cruz C., Bellmunt J., Burris H.A., Petrylak D.P., Teng S., et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014;515:558–562. doi: 10.1038/nature13904.
    1. FDA Atezolizumab for Urothelial Carcinoma. [(accessed on 10 December 2019)]; Available online: .
    1. Inman B.A., Longo T.A., Ramalingam S., Harrison M.R. Atezolizumab: A PD-L1–Blocking Antibody for Bladder Cancer. Clin. Cancer Res. 2017;23:1886–1890. doi: 10.1158/1078-0432.CCR-16-1417.
    1. FDA FDA Approves Bavencio (avelumab) for Metastatic Merkel Cell Carcinoma. [(accessed on 10 December 2019)]; Available online: .
    1. Apolo A.B., Infante J.R., Balmanoukian A., Patel M.R., Wang D., Kelly K., Mega A.E., Britten C.D., Ravaud A., Mita A.C., et al. Avelumab, an Anti–Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study. J. Clin. Oncol. 2017;35:2117–2124. doi: 10.1200/JCO.2016.71.6795.
    1. Rosenberg J.E., Hoffman-Censits J., Powles T., van der Heijden M.S., Balar A.V., Necchi A., Dawson N., O’Donnell P.H., Balmanoukian A., Loriot Y., et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial. Lancet. 2016;387:1909–1920. doi: 10.1016/S0140-6736(16)00561-4.
    1. AstraZeneca’s Imfinzi (durvalumab) Receives FDA Accelerated Approval for Previously Treated Patients with Advanced Bladder Cancer. [(accessed on 20 January 2020)]; Available online: .
    1. Powles T., O’Donnell P.H., Massard C., Arkenau H.-T., Friedlander T.W., Hoimes C.J., Lee J.L., Ong M., Sridhar S.S., Vogelzang N.J., et al. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma. JAMA Oncol. 2017;3:e172411. doi: 10.1001/jamaoncol.2017.2411.
    1. Zajac M., Boothman A.M., Ben Y., Gupta A., Jin X., Mistry A., Sabalos C., Nielsen A., Manriquez G., Barker C., et al. Analytical Validation and Clinical Utility of an Immunohistochemical Programmed Death Ligand-1 Diagnostic Assay and Combined Tumor and Immune Cell Scoring Algorithm for Durvalumab in Urothelial Carcinoma. Arch. Pathol. Lab. Med. 2018;143:722–731. doi: 10.5858/arpa.2017-0555-OA.
    1. Raja R., Kuziora M., Brohawn P., Higgs B.W., Gupta A., Dennis P.A., Ranade K. Early reduction in ctDNA predicts survival in lung and bladder cancer patients treated with durvalumab. Clin. Cancer Res. 2018 doi: 10.1158/1078-0432.CCR-18-0386.
    1. Bristol-Myers Squibb Receives FDA Approval for Opdivo (nivolumab) in Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma. [(accessed on 20 January 2020)]; Available online: .
    1. Sharma P., Callahan M.K., Bono P., Kim J., Spiliopoulou P., Calvo E., Pillai R.N., Ott P.A., de Braud F., Morse M., et al. Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): A multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. Lancet Oncol. 2016;17:1590–1598. doi: 10.1016/S1470-2045(16)30496-X.
    1. FDA Approves Merck’s Keytruda (pembrolizumab) for Certain Patients with Locally Advanced or Metastatic Urothelial Carcinoma. [(accessed on 20 January 2020)]; Available online: .
    1. Morsch R., Rose M., Maurer A., Cassataro M.A., Braunschweig T., Knüchel R., Vögeli T.A., Ecke T., Eckstein M., Weyerer V., et al. Therapeutic implications of PD-L1 expression in bladder cancer with squamous differentiation. BMC Cancer. 2020;20 doi: 10.1186/s12885-020-06727-2.
    1. Bellmunt J., de Wit R., Vaughn D.J., Fradet Y., Lee J.-L., Fong L., Vogelzang N.J., Climent M.A., Petrylak D.P., Choueiri T.K., et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N. Engl. J. Med. 2017;376:1015–1026. doi: 10.1056/NEJMoa1613683.
    1. Patterson K., Prabhu V., Xu R., Li H., Meng Y., Zarabi N., Zhong Y., Batteson R., Pellissier J., Keefe S., et al. Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. Eur. Urol. Oncol. 2019;2:565–571. doi: 10.1016/j.euo.2018.09.009.
    1. Jamieson N.B., Maker A.V. Gene-expression profiling to predict responsiveness to immunotherapy. Cancer Gene Ther. 2017;24:134–140. doi: 10.1038/cgt.2016.63.
    1. Janisch F., Yu H., Vetterlein M.W., Dahlem R., Engel O., Fisch M., Shariat S.F., Soave A., Rink M. Do Younger Patients with Muscle-Invasive Bladder Cancer have Better Outcomes? J. Clin. Med. 2019;8:1459. doi: 10.3390/jcm8091459.
    1. Ishii A., Yokoyama M., Tsuji H., Fujii Y., Tamaoka A. Pembrolizumab treatment of metastatic urothelial cancer without exacerbating myasthenia gravis. eNeurologicalSci. 2020;19 doi: 10.1016/j.ensci.2020.100236.
    1. Pollak M.N., Foulkes W.D., Mancuso J.G. Cancer immunoprevention: A case report raising the possibility of “immuno-interception”. Cancer Prev. Res. 2020;13:351–356. doi: 10.1158/1940-6207.CAPR-19-0528.
    1. Hojeij R., Domingos-Pereira S., Nkosi M., Gharbi D., Derré L., Schiller J., Jichlinski P., Nardelli-Haefliger D. Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer. Int. J. Mol. Sci. 2016;17:1125. doi: 10.3390/ijms17071125.
    1. Schulz W.A., Sørensen K.D. Epigenetics of Urological Cancers. Int. J. Mol. Sci. 2019;20:4775. doi: 10.3390/ijms20194775.
    1. Peggs K.S., Quezada S.A., Chambers C.A., Korman A.J., Allison J.P. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti–CTLA-4 antibodies. J. Exp. Med. 2009;206:1717–1725. doi: 10.1084/jem.20082492.
    1. van der Merwe P.A., Davis S.J. Molecular interactions mediating T cell antigen recognition. Annu. Rev. Immunol. 2003;21:659–684. doi: 10.1146/annurev.immunol.21.120601.141036.
    1. Carreno B.M., Bennett F., Chau T.A., Ling V., Luxenberg D., Jussif J., Baroja M.L., Madrenas J. CTLA-4 (CD152) Can Inhibit T Cell Activation by Two Different Mechanisms Depending on Its Level of Cell Surface Expression. J. Immunol. 2000;165:1352–1356. doi: 10.4049/jimmunol.165.3.1352.
    1. Obara W., Eto M., Mimata H., Kohri K., Mitsuhata N., Miura I., Shuin T., Miki T., Koie T., Fujimoto H., et al. A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder. Ann. Oncol. 2017;28:798–803. doi: 10.1093/annonc/mdw675.
    1. Yervoy Approval History. [(accessed on 22 January 2020)]; Available online: .
    1. Carthon B.C., Wolchok J.D., Yuan J., Kamat A., Ng Tang D.S., Sun J., Ku G., Troncoso P., Logothetis C.J., Allison J.P., et al. Preoperative CTLA-4 Blockade: Tolerability and Immune Monitoring in the Setting of a Presurgical Clinical Trial. Clin. Cancer Res. 2010;16:2861–2871. doi: 10.1158/1078-0432.CCR-10-0569.
    1. ElRazek E.A., Alhassanin S., Al Agizy H., Alhanafy A.M., Desoky E.H. Immunotherapy for advanced bladder cancer: A new era. Menoufia Med. J. 2019;32:8–13. doi: 10.4103/mmj.mmj_768_17.
    1. Ralph C., Elkord E., Burt D.J., O’Dwyer J.F., Austin E.B., Stern P.L., Hawkins R.E., Thistlethwaite F.C. Modulation of Lymphocyte Regulation for Cancer Therapy: A Phase II Trial of Tremelimumab in Advanced Gastric and Esophageal Adenocarcinoma. Clin. Cancer Res. 2010;16:1662–1672. doi: 10.1158/1078-0432.CCR-09-2870.
    1. European Association of Urology EAU Guidelines on Muscle Invasive and Metastatic Bladder Cancer. [(accessed on 29 April 2020)];2019 Available online: .
    1. Solsona E., Madero R., Chantada V., Fernandez J.M., Zabala J.A., Portillo J.A., Alonso J.M., Astobieta A., Unda M., Martinez-Piñeiro L., et al. Members of Club Urológico Español de Tratamiento Oncológico. Sequential combination of mitomycin C plus bacillus Calmette-Guérin (BCG) is more effective but more toxic than BCG alone in patients with non-muscle-invasive bladder cancer in intermediate- and high-risk patients: Final outcome of CUETO 93009, a randomized prospective trial. Eur. Urol. 2015;67:508–516. doi: 10.1016/j.eururo.2014.09.026.
    1. Kaasinen E., Wijkström H., Rintala E., Mestad O., Jahnson S., Malmström P.U. Seventeen-year follow-up of the prospective randomized Nordic CIS study: BCG monotherapy versus alternating therapy with mitomycin C and BCG in patients with carcinoma in situ of the urinary bladder. Scand. J. Urol. 2016;50:360–368. doi: 10.1080/21681805.2016.1210672.
    1. Shepherd A.R., Shepherd E., Brook N.R. Intravesical Bacillus Calmette-Guérin with interferon-alpha versus intravesical Bacillus Calmette-Guérin for treating non-muscle-invasive bladder cancer. Cochrane Database Syst. Rev. 2017;3:CD012112. doi: 10.1002/14651858.CD012112.pub2.
    1. Di Stasi S.M., Giannantoni A., Giurioli A., Valenti M., Zampa G., Storti L., Attisani F., De Carolis A., Capelli G., Vespasiani G., et al. Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: A randomised controlled trial. Lancet Oncol. 2006;7:43–51. doi: 10.1016/S1470-2045(05)70472-1.
    1. Cui J., Wang W., Chen S., Chen P., Yang Y., Guo Y., Zhu Y., Chen F., Shi B. Combination of Intravesical Chemotherapy and Bacillus Calmette-Guerin Versus Bacillus Calmette-Guerin Monotherapy in Intermediate- and High-risk Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-analysis. Medicine. 2016;95:e2572. doi: 10.1097/MD.0000000000002572.
    1. Yin M., Joshi M., Meijer R.P., Glantz M., Holder S., Harvey H.A., Kaag M., Fransen van de Putte E.E., Horenblas S., Drabick J.J. Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: A Systematic Review and Two-Step Meta-Analysis. Oncologist. 2016;21:708–715. doi: 10.1634/theoncologist.2015-0440.
    1. Advanced Bladder Cancer Meta-Analysis Collaboration Neoadjuvant chemotherapy in invasive bladder cancer: A systematic review and meta-analysis. Lancet. 2003;361:1927–1934. doi: 10.1016/S0140-6736(03)13580-5.
    1. Winquist E., Kirchner T.S., Segal R., Chin J., Lukka H., Genitourinary Cancer Disease Site Group. Cancer Care Ontario Program in Evidence-based Care Practice Guidelines Initiative Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: A systematic review and meta-analysis. J. Urol. 2004;131:561–569. doi: 10.1097/01.ju.0000090967.08622.33.
    1. Advanced Bladder Cancer (ABC) Meta-analysis Collaboration Neoadjuvant chemotherapy in invasive bladder cancer: Update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur. Urol. 2005;48:202–205. doi: 10.1016/j.eururo.2005.04.006.
    1. Pinto-Leite R., Arantes-Rodrigues R., Sousa N., Oliveira P.A., Santos L. mTOR inhibitors in urinary bladder cancer. Tumor Biol. 2016;37:11541–11551. doi: 10.1007/s13277-016-5083-1.
    1. Everolimus (Afinitor) [(accessed on 30 January 2020)]; Available online: .
    1. Chiong E., Lee I.-L., Dadbin A., Sabichi A.L., Harris L., Urbauer D., McConkey D.J., Dickstein R.J., Cheng T., Grossman H.B. Effects of mTOR Inhibitor Everolimus (RAD001) on Bladder Cancer Cells. Clin. Cancer Res. 2011;17:2863–2873. doi: 10.1158/1078-0432.CCR-09-3202.
    1. Vasconcelos-Nóbrega C., Pinto-Leite R., Arantes-Rodrigues R., Ferreira R., Brochado P., Cardoso M.L., Palmeira C., Salvador A., Guedes-Teixeira C.I., Colaço A., et al. In vivo and in vitro effects of RAD001 on bladder cancer. Urol. Oncol. Semin. Orig. Investig. 2013;31:1212–1221. doi: 10.1016/j.urolonc.2011.11.002.
    1. Milowsky M.I., Iyer G., Regazzi A.M., Al-Ahmadie H., Gerst S.R., Ostrovnaya I., Gellert L.L., Kaplan R., Garcia-Grossman I.R., Pendse D., et al. Phase II study of everolimus in metastatic urothelial cancer. BJU Int. 2013;112:462–470. doi: 10.1111/j.1464-410X.2012.11720.x.
    1. Pinto-Leite R., Arantes-Rodrigues R., Palmeira C., Colaço B., Lopes C., Colaço A., Costa C., da Silva V.M., Oliveira P., Santos L. Everolimus combined with cisplatin has a potential role in treatment of urothelial bladder cancer. Biomed. Pharmacother. 2013;67:116–121. doi: 10.1016/j.biopha.2012.11.007.
    1. Smith S.G., Baltz J.L., Koppolu B.P., Ravindranathan S., Nguyen K., Zaharoff D.A. Immunological mechanisms of intravesical chitosan/interleukin-12 immunotherapy against murine bladder cancer. Oncoimmunology. 2017;6:e1259050. doi: 10.1080/2162402X.2016.1259050.
    1. Smith S.G., Koppolu B.P., Ravindranathan S., Kurtz S.L., Yang L., Katz M.D., Zaharoff D.A. Intravesical chitosan/interleukin-12 immunotherapy induces tumor-specific systemic immunity against murine bladder cancer. Cancer Immunol. Immunother. 2015;64:689–696. doi: 10.1007/s00262-015-1672-x.
    1. Liu X., Wu Y., Zhou Z., Huang M., Deng W., Wang Y., Zhou X., Chen L., Li Y., Zeng T., et al. Celecoxib inhibits the epithelial-to-mesenchymal transition in bladder cancer via the miRNA-145/TGFBR2/Smad3 axis. Int. J. Mol. Med. 2019;44:683–693. doi: 10.3892/ijmm.2019.4241.
    1. Aragon-Ching J.B., Trump D.L. Targeted therapies in the treatment of urothelial cancers. Urol. Oncol. Semin. Orig. Investig. 2017;35:465–472. doi: 10.1016/j.urolonc.2017.03.011.
    1. Bladder Cancers Respond to EGFR Inhibitors. Cancer Discov. 2014;4:980–981.
    1. Hussain M., Daignault S., Agarwal N., Grivas P.D., Siefker-Radtke A.O., Puzanov I., MacVicar G.R., Levine E.G., Srinivas S., Twardowski P., et al. A randomized phase 2 trial of gemcitabine/cisplatin with or without cetuximab in patients with advanced urothelial carcinoma. Cancer. 2014;120:2684–2693. doi: 10.1002/cncr.28767.
    1. Iqbal N., Iqbal N. Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol. Biol. Int. 2014;2014 doi: 10.1155/2014/852748.
    1. Peethambaram P.P., Melisko M.E., Rinn K.J., Alberts S.R., Provost N.M., Jones L.A., Sims R.B., Lin L.R.C., Frohlich M.W., Park J.W. A phase I trial of immunotherapy with lapuleucel-T (APC8024) in patients with refractory metastatic tumors that express HER-2/neu. Clin. Cancer Res. 2009;15:5937–5944. doi: 10.1158/1078-0432.CCR-08-3282.
    1. Curti B.D., Kovacsovics-Bankowski M., Morris N., Walker E., Chisholm L., Floyd K., Walker J., Gonzalez I., Meeuwsen T., Fox B.A., et al. OX40 Is a Potent Immune-Stimulating Target in Late-Stage Cancer Patients. Cancer Res. 2013;73:7189–7198. doi: 10.1158/0008-5472.CAN-12-4174.
    1. Aghaalikhani N., Rashtchizadeh N., Shadpour P., Allameh A., Mahmoodi M. Cancer stem cells as a therapeutic target in bladder cancer. J. Cell. Physiol. 2019;234:3197–3206. doi: 10.1002/jcp.26916.
    1. Jinesh G.C., Choi W., Shah J.B., Lee E.K., Willis D.L., Kamat A.M. Blebbishields, the emergency program for cancer stem cells: Sphere formation and tumorigenesis after apoptosis. Cell Death Differ. 2013;20:382–395. doi: 10.1038/cdd.2012.140.
    1. Poch M., Hall M., Joerger A., Kodumudi K., Beatty M., Innamarato P.P., Fishman M.N., Zhang J., Sexton W.J., Pow-Sang J.M., et al. Expansion of tumor infiltrating lymphocytes (TIL) from bladder cancer. Oncoimmunology. 2018;7:e1476816. doi: 10.1080/2162402X.2018.1476816.
    1. Parriott G., Deal K., Crean S., Richardson E., Nylen E., Barber A. T cells expressing a chimeric-PD1-Dap10-CD3zeta receptor reduce tumor burden in multiple murine syngeneic models of solid cancer. Immunology. 2020 doi: 10.1111/imm.13187.
    1. Meneses-Gutiérrez C.L., Hernández-Damián J., Pedraza-Chaverri J., Guerrero-Legarreta I., Téllez D.I., Jaramillo-Flores M.E. Antioxidant Capacity and Cytotoxic Effects of Catechins and Resveratrol Oligomers Produced by Enzymatic Oxidation against T24 Human Urinary Bladder Cancer Cells. Antioxidants. 2019;8:214. doi: 10.3390/antiox8070214.
    1. Rutz J., Maxeiner S., Justin S., Bachmeier B., Bernd A., Kippenberger S., Zöller N., Chun F.-H., Blaheta R.A. Low Dosed Curcumin Combined with Visible Light Exposure Inhibits Renal Cell Carcinoma Metastatic Behavior in Vitros. Cancers. 2020;12:302. doi: 10.3390/cancers12020302.
    1. Roos F., Binder K., Rutz J., Maxeiner S., Bernd A., Kippenberger S., Zöller N., Chun F.K.-H., Juengel E., Blaheta R.A. The Antitumor Effect of Curcumin in Urothelial Cancer Cells Is Enhanced by Light Exposure In Vitro. Evid.-Based Complementary Altern. Med. 2019;2019:6374940. doi: 10.1155/2019/6374940.
    1. Juengel E., Erb H.H.H., Haferkamp A., Rutz J., Chun F.K.H., Blaheta R.A. Relevance of the natural HDAC inhibitor sulforaphane as a chemopreventive agent in urologic tumors. Cancer Lett. 2018;435:121–126. doi: 10.1016/j.canlet.2018.07.017.
    1. Aggarwal B.B., Vijayalekshmi R.V., Sung B. Targeting Inflammatory Pathways for Prevention and Therapy of Cancer: Short-Term Friend, Long-Term Foe. Clin. Cancer Res. 2009;15:425–430. doi: 10.1158/1078-0432.CCR-08-0149.
    1. Wawruszak A., Luszczki J.J., Kalafut J., Okla K., Halasa M., Rivero-Muller A., Stepulak A. Additive Pharmacological Interaction between Cisplatin (CDDP) and Histone Deacetylase Inhibitors (HDIs) in MDA-MB-231 Triple Negative Breast Cancer (TNBC) Cells with Altered Notch1 Activity—An Isobolographic Analysis. Int. J. Mol. Sci. 2019;20:3663. doi: 10.3390/ijms20153663.
    1. Eckschlager T., Plch J., Stiborova M., Hrabeta J. Histone Deacetylase Inhibitors as Anticancer Drugs. Int. J. Mol. Sci. 2017;18:1414. doi: 10.3390/ijms18071414.
    1. Juengel E., Najafi R., Rutz J., Maxeiner S., Makarevic J., Roos F., Tsaur I., Haferkamp A., Blaheta R.A. HDAC inhibition as a treatment concept to combat temsirolimus-resistant bladder cancer cells. Oncotarget. 2017;8:110016–110028. doi: 10.18632/oncotarget.22454.
    1. Mastuo T., Miyata Y., Yuno T., Mukae Y., Otsubo A., Mitsunari K., Ohba K., Sakai H. Molecular Mechanisms of the Anti-Cancer Effects of Isothiocyanates from Cruciferous Vegetables in Bladder Cancer. Molecules. 2020;25:575. doi: 10.3390/molecules25030575.
    1. Tang L., Zirpoli G.R., Guru K., Moysich K.B., Zhang Y., Ambrosone C.B., McCann S.E. Consumption of Raw Cruciferous Vegetables is Inversely Associated with Bladder Cancer Risk. Cancer Epidemiol. Biomarkers Prev. 2008;17:938–944. doi: 10.1158/1055-9965.EPI-07-2502.
    1. Liu B., Mao Q., Lin Y., Zhou F., Xie L. The association of cruciferous vegetables intake and risk of bladder cancer: A meta-analysis. World J. Urol. 2013;31:127–133. doi: 10.1007/s00345-012-0850-0.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren